It is often desirable to therapeutically activate excitable tissue, such as nerve, muscle, or glandular cells of a patient by electrical stimulation or via medications. An undesirable side effect of such therapeutic activation of excitable tissue is that other tissue, either nearby or distant, may be undesirably activated, either directly by the same mode of activation, or indirectly by sensory feedback or other reflexes.
Generally, undesired action potentials in sensory nerves or dorsal roots may either be disagreeable to the patient or cause contrary effects. When stimulating to assist peristalsis in the esophagus, ureter, stomach, or intestine, co-contraction of sphincters or disagreeable sensations or reverse peristalsis might be undesirable. For instance, if a patient is unable to control urination or defecation, stimulation of peripheral nerves or ventral roots to contract a patient's bladder for micturition or to move bowel contents may be desirable. Such activation, or even lower amplitude stimulation, however, will typically create action potentials in sphincters, such as those in the external urethra or anus. Such action potentials will tend to cause the sphincters to contract, which may result in an inability to pass urine or fecal matter beyond the sphincters. In addition, increased pressure in the bladder caused by simultaneous compression of the patient's bladder and contraction of the patient's external urethral sphincter may lead to injury to the patient, including increased pressure and damage to either or both the bladder and the kidneys. A conventional approach that has been proposed for patients that are substantially paralyzed is to cut the patient's nerves that lead back into the spinal cord (dorsal roots) so that the stimulation of the bladder does not cause a lot of neural activity in the spinal cord. If a patient's bladder is significantly overfilled, autonomic dysreflexia may occur causing a very large and dangerous increase in the patient's blood pressure, which may cause a stroke.
When stimulating to defibrillate a patient's heart, extremely intense pain is typically inflicted upon the patient due to simultaneous activation of many afferent fibers, some of which may even be the axons of nociceptors.
When stimulating certain motorneurons, activations directly or by spinal reflex of antagonistic motorneurons and muscles may interfere with the desired motion, necessitating an increase in the strength of stimulation, which causes increased rigidity of a patient's joints.
Electrical excitation of tissue at low frequencies (e.g., less than 100 Hertz) has been known to cause action potentials in nerve and muscle. In addition, some techniques have been described to block action potentials in certain nerve fibers, with the best observations done in animal experiments.
Tanner (Nature, vol. 195, 1962: 712-713) and Woo & Campbell (Bull. L. A. Neurol. Soc., vol. 29, 1964:87-94) showed that 20,000 Hz stimulation of a nerve is able to block passing action potentials, with larger voltages (amplitudes) needed to progressively block smaller fibers. Recently, from therapeutic stimulation of the brain in patients with tremor and other symptoms of Parkinson's disease, evidence has mounted that high frequency stimulation (100-185 Hertz) keeps neurons depolarized, and hence incapable of producing action potentials (Benabid et al., Lancet, vol. 337, 1991: 403-406; Benazzouz et al., Neurosci. Lett., vol. 189, 1995: 77-80). High frequency stimulation of the spinal cord or nerves (250 Hertz and more) has been anecdotally reported to relieve chronic pain, but whether this works by blocking of action potentials is unknown (Picaza et al., Surg. Neurol., vol. 4, 1975: 105-114 and 115-126; Sheldon et al., Surg. Neurol., vol. 4, 1975: 127-132; Bennett et al., Neuromodulation, vol. 2, 1999: 202-210).
Mendel & Wall (J. Physiol., vol. 172, 1964: 274-294) and Campbell & Woo (Bull. Los Angeles Neurol. Soc., vol. 31, 1966: 63-71) demonstrated a similar amplitude-dependent blocking of action potentials in progressively smaller axons using direct current (D.C.) signals. Recently, evidence has developed that repetitive stimulation in rats of the brain area called the amygdala, which can cause seizures due to kindling, can have its kindling effects quenched by use of 5 to 15 microampere D.C. currents applied once a day for 15 minutes (Weiss et al., Exper. Neurol., vol. 154, 1998: 185-192).
The disadvantage of direct current pulses is that they can lead to tissue or electrode damage (Pudenz, et al, Surg. Neurol., vol. 4, 1975:265-270) or to asynchronous repetitive action potential discharges (Manfredi, Arch. Ital. Biol., vol 108, 1970: 52-71; Sassen & Zimmerman, Pflugers Arch. Gesamte Physiol. Menschen Tiere, vol. 341, 1973: 179-195).
Van den Honert & Mortimer (IEEE trans. BME., vol. 28, 1981: 373-378 and 379-382) developed a technique to create action potentials that propagate in only one direction along axons using a tripolar cuff with three electrodes and two regulated current stimulators. This method was used by Brindley & Craggs (J. Neurol. Neurosurg. Psychiat., vol. 43, 1980: 1083-1090) to excite only the smaller (parasympathetic) fibers in spinal nerve roots and peripheral nerves for bladder emptying. Ungar, Mortimer & Sweeney (Ann. Biomed. Engng, vol. 14, 1986: 437-450) were also able to generate unidirectionally propagating action potentials in nerves using an asymmetric monopolar electrode cuff. However, both of these partial-blocking techniques require complete encirclement of the axons of interest with non-conducting materials, something which the high frequency and D.C. techniques do not require.
In order to minimize undesirable side effects associated with therapeutic activation of tissue, including, but not limited to, the side effects mentioned above, it may be desirable to deactivate or inhibit certain excitable tissue during the time that the desired effect is being produced in the therapeutically activated tissue.
It would, therefore, be desirable to block action potentials in tissue that are deliberately generated from low frequency stimulation. The block may not be complete, and there may be asynchronous, even repetitive generation of some action potentials in the process, but under certain circumstances, it may be possible to prevent most of the action potentials in certain nerves that otherwise may be caused by other electrodes in nearby tissue that use deliberate low frequency pulses to cause action potentials. The volume of tissue recruited near the deliberate “activation” electrodes and the volume of tissue inhibited near the “blocking” electrodes would both depend upon the parameters of stimulation, especially the amplitude and pulse width.